Colchicine Modulates the Actin Cytoskeleton by DirectBinding to the Monomer and Facilitating Polymerization

Haciosmanoglu Aldogan, Ebru and Günçer, Başak and Baday, Sefer and Özerman Edis, Bilge and Mártonfalvi, Zsolt and Agócs, Gergely and Hollósi, Anna and Varga, Andrea and Tordai, Hedvig and Kellermayer, Miklós and Gül, Ahmet and Bektaş, Muhammet (2025) Colchicine Modulates the Actin Cytoskeleton by DirectBinding to the Monomer and Facilitating Polymerization. FASEB Journal, 39 (19). No. e71054. (In Press)

Text The FASEB Journal - 2025 - Aldogan - Colchicine Modulates the Actin Cytoskeleton by Direct Binding to the Monomer and.pdf - Published Version Restricted to Repository staff only Download (2MB)

Abstract

Actin, the most abundant intracellular protein, exists in a monomeric globular form (G-actin) or as polymerized filamentousactin (F-actin), and is essential for cell morphology, motility, and intracellular transport. Colchicine is a well- established anti-inflammatory drug primarily known for binding tubulin and inhibiting microtubule polymerization, yet its full mechanism ofaction remains unclear. Here, we investigated whether colchicine directly modulates actin cytoskeleton dynamics. Using humanmonocytic and murine B-lymphoma cell lines, combined with in vitro biochemical and biophysical assays, we found that col-chicine binds directly to G-actin with submicromolar affinity, enhances actin polymerization, and stabilizes F-actin. Colchicinetreatment in cells shifted the F−/G-actin ratio toward the filamentous form, increased cortical actin organization, and alteredcell mechanical properties. Thermal shift assays confirmed increased actin stability, while molecular docking identified two po-tential colchicine-binding sites—one at the ATP-binding cleft in G-actin and another at the intermonomeric interface in F-actin.These findings reveal a previously unrecognized actin-modulatory role of colchicine, providing mechanistic insight into its anti-inflammatory effects and suggesting potential applications in diseases involving actin cytoskeletal dysregulation.

Actions (login required)

Edit Item